This is the first competing renewal application for Yale University School of Medicine's Vascular Research Postdoctoral Training Grant. The goal of this program is to provide laboratory and translational research training for highly qualified physician (M.D. and M.D./Ph.D.) and Ph.D. postdoctoral fellows in vascular biology, in preparation for careers as independent investigators in blood vessel biology- and medicine-related disciplines. Selection of trainees will be based on a demonstrated commitment to vascular biology and strong prior research experience or potential of same. Applications will be encouraged from both clinical and basic science departments, with a nationwide competition for the 7 yearly slots. Minority applicants will be specifically solicited. The training will be mentor-based, also including both advisory committees and didactic courses. The minimum duration of training per fellow will be 2 years, with the majority of fellows remaining in the program for 3 years. The Cardiovascular Medicine Division of Internal Medicine and Yale's Interdisciplinary Program in Vascular Biology and Transplantation will be the central foundations for the program. In fact, a key asset to this training program is Yale's interdisciplinary strength in vascular biology. Departmental affiliations for the primary participating faculty include Internal Medicine (Cardiovascular Medicine, Pulmonary and Critical Care Medicine), Immunobiology, Pharmacology, Molecular, Cellular and Developmental Biology, Pathology, Genetics, Bioengineering, Cellular and Molecular Physiology, Epidemiology and Public Health and Cardiothoracic Surgery. This is a testimony to the wide spectrum of strong vascular biology laboratories at Yale and the institutional nature of the program. The faculty was chosen based on impressive histories of mentorship, ongoing vascular research productivity, strong extramural support and commitment to serve as mentors within the program. Examples of vascular research opportunities include: (1) molecular determinants and consequences of leukocyte-endothelial cell interactions;(2) microcirculatory analysis of neurohumoral and cell coupling mechanisms which control vasomotion;(3) molecular imaging of angiogenesis and vascular remodeling utilizing nuclear and MR imaging in animal models;(4) mapping and identification of genes that contribute to the development of vascular disease (arterio-venous malformation, coronary artery disease) in humans, through molecular genetic techniques;(5) engineering of vascular biomaterials, and molecular determinants of healing responses post-implantation;(6) effects of inflammation and reactive oxygen species generation on endothelial homeostasis;(7) regulators of endothelial dysfunction in human disease states, such as congestive heart failure;and (8) generation of angiogenic gene regulators for use in clinical trials. As described, this represents a wide range of disease-related vascular research, with key translational components. Trainee progress will be monitored by each mentor, the trainee's advisory committee and the Program Director. It is the expectation that, through this program, we will train future national and international leaders in vascular research. Cardiovascular disease is the leading cause of death in the U.S., and a major cause of morbidity and mortality world-wide. This program will provide important opportunities for individuals from multiple disciplines to eventually lead high impact efforts at reducing the incidence of, and improving outcomes in, cardiovascular disease. (End of Abstract)